Deoxyspergualin (DSP) is a potent immunosuppressive drug that is able
to both prevent and reverse acute allograft rejection. Although there
is good evidence that DSP can inhibit T and B lymphocyte responses, th
e effect of this drug upon monocyte function is controversial. In the
current study, substantial local proliferation of inflammatory macroph
ages (41.6+/-5.5% of ED1(+) cells) within acutely rejecting rat renal
allografts was identified by expression of the proliferating cell nucl
ear antigen. Treatment of animals with DSP not only reduced macrophage
accumulation within the tissue, but it also significantly inhibited l
ocal proliferation of macrophages within the graft (26.4+/-5.6% of ED1
(+) cells, P<0.05 vs. untreated). This appeared to be, at least in par
t, a direct effect of DSP upon macrophages since the drug also inhibit
ed growth of 2 monocytic cell lines (RC-2A and U937) in vitro. However
, DSP treatment had no effect upon LPS-induced monocyte IL-1 beta, TNF
alpha, and IL-6 mRNA and protein production, indicating that this dru
g is not a general inhibitor of monocyte function. In conclusion, this
study has demonstrated that local proliferation of macrophages within
the kidney is a prominent feature of acute allograft rejection and th
at inhibition of this response is one mechanism whereby DSP exerts its
potent immunosuppressive actions.